Major depressive disorder (MDD) - PowerPoint Presentation

1. Major depressive disorder (MDD)Comorbidity

2. Major depressive disorder (MDD)Prevalence of chronic conditions in patients with MDDA retrospective analysis of patient data was performed to compare the prevalence of chronic conditions in patients with depression and the general population1Of the total population studied, roughly one in ten had depression1Within the population with depression, the presence of depression was found to be significantly associated with:1COPD=chronic obstructive pulmonary disorder; MDD=major depressive disorderBhattacharya et al. BMC Psychiatry 2014;14:102Depression is a risk factor for a range of physical conditions1ArthritisAsthmaCOPDDiabetesHeart diseaseHypertension

3. Major depressive disorder (MDD)Prevalence of MDD in patients with chronic conditionsDepression is comorbid with many conditions, with low mood sometimes representing a natural reaction to any disabling condition1-3A systematic literature review, covering the period 1992–2012, examined the evidence for MDD in various chronic conditions3They found robust evidence for a relationship between various chronic conditions and MDD, as shown in the graph3Depression appears to negatively contribute to the development of chronic illnesses, just as chronic illnesses negatively affect the prognosis of depression3These results reinforce, in the authors’ minds, the need for a synergistic approach to the treatment of depression that takes into account all the needs of the patient3Prevalence of depression in chronic illnesses3MDD=major depressive disorderAPA. DSM-5. 2013Buckley et al. Schizophr Bull 2009;35(2):383–402Voinov et al. Prim Care Companion CNS Disord 2013;15(2):PCC.12r014683A range of chronic conditions appear to increase the risk of MDD3DiabetesCancerHeart diseaseStrokeGeneralpopulation100203040506070Prevalence of depression (%)

4. Mean health score (0–100)Major depressive disorder (MDD)Depression adds to the burden of chronic conditionsAdapted from: Moussavi et al. Lancet 2007;370(9590):851–8584Global mean health by disease status1Depression adds to the burden of chronic conditionsWith depressionWithout depression

5. Major depressive disorder (MDD)The effect of comorbidities on patients’ quality of lifePatients with MDD and comorbid GAD have significantly reduced quality of life (as assessed by the WHOQOL-BREF) compared with those without comorbid GAD1Patients with MDD and comorbid panic disorder show significantly reduced quality of life (as assessed by the Q-LES-Q) compared with patients without comorbid panic disorder2General medical conditions also have a negative effect on quality of life when they are comorbid with MDD; compared with MDD patients without comorbid general medical conditions, those with comorbid general medical conditions show significantly reduced quality of life scores3The comorbidities of depression should be taken into account when treatment options are being considered4GAD=generalised anxiety disorder; MDD=major depressive disorder; Q-LES-Q=Quality of Life Enjoyment and Satisfaction Questionnaire; WHOQOL-BREF=World Health Organization Quality of Life Scale – Brief1. Zhou et al. Sci Rep 2017;7:405112. IsHak et al. Depress Anxiety 2014;31(8):707–7163. IsHak et al. Psychopharmacol Bull 2018;48(1):8–254. APA. Practice guideline for the treatment of patients with major depressive disorder. 20105The comorbidities of MDD have a negative impact on a patient’s quality of life1-3

6. Neuropsychiatric comorbiditiesMajor depressive disorder (MDD)6

7. Major depressive disorder (MDD)Psychiatric comorbidities of MDDMDD frequently occurs alongside substance-related disorders, and anxiety disorders, as well as a host of other psychiatric conditions1In one study of 190 patients with MDD, roughly a third had one or more psychiatric comorbidity, including anxiety disorders2In an analysis of comorbidity seen in the STAR*D study of patients with depression, the presence of one anxiety disorder was highly related to the presence of another – only a minority of patients had a single diagnosis – one diagnosis appeared to increase the risk of a second diagnosis, and so on3The National Comorbidity Survey, conducted in the United States in the early 1990s, interviewed >8,000 patients, and found that a depressive episode significantly increased the risk of subsequent DSM-III comorbidity:4,5Generalised anxiety disorder OR=3.4Panic disorder OR=5.1Illicit drug dependence OR=4.3Post-traumatic stress disorder OR=6.7Social phobia OR=2.9Alcohol dependence OR=3.3DSM-III=Diagnostic and Statistical Manual of Mental Disorders – Third edition; MDD=major depressive disorder; OR=odds ratio; STAR*D=Sequenced Treatment Alternatives to Relieve DepressionAPA. DSM-5. 2013Thaipisuttikul et al. Neuropsychiatr Dis Treat 2014;10:2097–2103Rush et al. J Affect Disord 2005;87(1):43–55;Kessler et al. Arch Gen Psychiatry 1994;51(1):8–19Kessler. The prevalence of psychiatric comorbidity. 19977Psychiatric comorbidities are common in patients with MDD, especially anxiety and other mood disorders1,2

8. Major depressive disorder (MDD)AnxietyGAD and excessive worry are commonly seen in patients with MDD – depending on study methodology, up to 50% of patients with MDD have a diagnosis of an anxiety disorder1-4The presence of a major depressive episode increases the risk of GAD by 3.4 times5Generalised anxiety/worry is a common feature of depressive disorders, but should be diagnosed separately if the excessive worry has occurred outside the course of the depressive illness1In the large-scale STAR*D study, anxious depression was associated with poorer acute outcomes following antidepressant treatment than non-anxious depression2In an independent analysis, the presence of anxiety symptoms in patients with MDD was associated with worse depression scores, as measured by the PHQ-9 scale4Comparison of PHQ-9 scores in patients with MDD by GAD status4***p<0.001 vs MDD only GAD=generalised anxiety disorder; MDD=major depressive disorder; PHQ-9=Patient Health Questionnaire – 9 items; STAR*D=Sequenced Treatment Alternatives to Relieve DepressionAPA. DSM-5. 2013Fava et al. Am J Psychiatry 2008;165(3):342–351Fava et al. Compr Psychiatry 2000;41(2):97–102 Zhou et al. Sci Rep 2017;7:40511; 5. Kessler. The prevalence of psychiatric comorbidity. 19978***

9. Major depressive disorder (MDD)Obsessive–compulsive disorder (OCD)Lifetime comorbidity rates of OCD and MDD up to 60% have been reported,1-3 compared with an OCD prevalence rate of 1.6% in the general population4 – up to 37.5 times greaterThere is disagreement about whether the severity of depressive symptoms and the severity of OCD symptoms are correlated, with a wide range of comorbidity values of OCD and MDD reported1,2In one study of >1,300 patients with MDD, the phenotypes with and without OCD were compared, and showed a significantly poorer prognosis for the patients with comorbid OCD2MDD=major depressive disorder; OCD=obsessive–compulsive disorderRickelt et al. J Affect Disord 2016;203:241–247Dold et al. J Affect Disord 2018;227:254–259Thaipisuttikul et al. Neuropsychiatr Dis Treat 2014;10:2097–2103Kessler et al. Arch Gen Psychiatry 2005;62(6):593–6029

10. Major depressive disorder (MDD)Post-traumatic stress disorder (PTSD)The risk of experiencing a traumatic event is higher in patients with MDD, which may explain the fact that they are at higher risk of developing PTSD1-3A diagnosis of major depressive disorder, rather than PTSD, should be made if the patient’s low mood was not preceded by a traumatic event, and other symptoms of PTSD are not present3The presence of a major depressive episode increases the risk of PTSD by 6.7 times4One study compared the HAM-D scores of patients with PTSD (n=59) and those of healthy controls (n=162) and found:1Patients with lifetime PTSD were more likely to be female, non-white, not be married, and to have fewer years of education1As shown in the graph, patients with PTSD scored significantly higher on the HAM-D scale1Comparison of HAM-D scores in patients with MDD by PTSD status1*p<0.05 versus MDD onlyHAM-D=Hamilton depression rating scale; MDD=major depressive disorder; PTSD=post-traumatic stress disorderOquendo et al. Am J Psychiatry 2005;162(3):560–566Fullerton et al. J Nerv Ment Dis 2000;188(5):267–272APA. DSM-5. 2013Kessler. The prevalence of psychiatric comorbidity. 199710PTSD is frequently comorbid with depression1*

11. Increased risk, no symptomsMild or non-specific symptomsModerate but sub-threshold symptomsFirst episode Severe, persistent, or unremitting illnessIncomplete remission, relapse, or multiple relapsesMajor depressive disorder (MDD)Attention deficit hyperactivity disorder (ADHD)MDD and ADHD are often seen clinically as comorbid disorders, with prevalence rates as high as 50%1-3Current MDD increases the risk of probable ADHD by 4.5 times4ADHD is a distinct diagnosis from MDD because, in MDD, difficulty with concentration becomes prominent during a depressive episode5Interestingly, as shown in the graph, the prevalence of ADHD symptoms appears to be linked to the clinical stage of MDD, with a peak of prevalence during Stage 4 (chronic depressive disorder, characterised by severe, persistent, or unremitting illness)4In one study, patients with MDD and ADHD had a higher frequency of generalised anxiety disorder and social phobia, when compared to patients with ADHD alone6ADHD symptom prevalence across clinical stages of MDD4,7ADHD=attention deficit hyperactivity disorder; MDD=major depressive disorderKatzman et al. BMC Psychiatry 2017;17:302Torgersen et al. Nord J Psychiatry 2006;60(1):38–43Kessler et al. Am J Psychiatry 2006;163(4):716–723Bron et al. J Affect Disord 2016;197:29–35APA. DSM-5. 2013Fischer et al. J Psychiatr Res 2007;41(12):991–996; 7. McGorry et al. Aust N Z J Psychiatry 2006;40(8):616–622110510152025ADHD prevalence (%)01A1B234Clinical stages of MDD7

12. Major depressive disorder (MDD)SchizophreniaIn the National Comorbidity Survey, lifetime comorbidity of a major depressive episode and non-affective psychosis had an odds ratio of 7.01In patients with co-occurring MDD and schizophrenia, the severity of depression scores has been shown to be correlated with the severity of the psyhosis2Interestingly, elevated rates of depression have been documented in patients in the prodrome of schizophrenia2,3Some of the diagnostic criteria for depression overlap with those of schizophrenia, e.g., anhedonia, amotivational and avolitional states, and social withdrawal,5 leading to the argument that depression should rather be considered part of schizophrenia2To distinguish schizophrenia and MDD, the temporal relationship between the mood disturbance and the psychosis should be considered; if the delusions or hallucinations occur exclusively during a depressive episode, then the diagnosis is MDD with psychotic features5MDD=major depressive disorderKessler. The prevalence of psychiatric comorbidity. 1997Chiappelli et al. Schizophr Res 2014;159(1):243–248Upthegrove. Adv Psychiatr Treat 2009;15:372–379Castle & Bosanac. Adv Psychiatr Treat 2012;18:280–288APA. DSM-5. 201312Depression is common in first-episode psychosis, and is related to poorer treatment outcome3

13. Major depressive disorder (MDD)Substance-use disorderSeveral lines of evidence have shown that patients with depression have higher rates of substance-use disorders than the general population1,2The presence of a major depressive episode increases the risk of drug dependence by 4.3 times3In an analysis of the STAR*D study data, patients with MDD and comorbid substance-use disorder were more likely to:4Have earlier onset of depressionExperience greater depressive symptomatologyExperience greater functional impairmentHave a greater suicide riskDepressive disorder can be as a result of substance or medication use: a differential diagnosis is made based on whether a substance is aetiologically related to the mood disturbance5The hypothetical links between depression and substance-use disorder1MDD=major depressive disorder; STAR*D=Sequenced Treatment Alternatives to Relieve DepressionRappeneau & Bérod. Neurosci Biobehav Rev 2017;77:303–316Tolliver & Anton. Dialogues Clin Neurosci 2015;17(2):181–190Kessler. The prevalence of psychiatric comorbidity. 1997Davis et al. Am J Addict 2006;15(4):278–285APA. DSM-5. 201313Direct causal relationshipDepressionSubstance-use disorderWithdrawal,latent pre-dispositionShared risk factorsGenetic predisposition, and/or social and environmental factorsCoping with dysphoric moods

14. Major depressive disorder (MDD)Neurological disorders and MDDDepression appears to increase the risk of several neurological disorders, including Parkinson’s disease and Alzheimer’s disease1-3In one nested-case cohort study, for up to 25 years after a depressive episode the risk of Parkinson’s disease was elevated1There is some disagreement, however, about the extent that depression constitutes a risk factor for neurological diseases, and the extent that depression may be part of the prodrome of those conditions1It has been hypothesised that the aetiology of MDD and neurological disorders share a common theme of oxidative stress, and this explains the connection between these conditions2These shared pathways centre around:2Inflammatory cytokinesThe hypothalamic–pituitary–adrenal axisCortisolReactive oxygen species and free radicalsAlthough still hypothetical, it is proposed that an individual experiencing a high oxidative stress burden will progress to either MDD, or neurological disease, based on genetic vulnerability2MDD=major depressive disorderGustafsson et al. Neurology 2015;84(24):2422–2429; Rodrigues et al. Cell Mol Neurobiol 2014;34(7):925–949; Wilson et al. Neurology 2014;83(8):702–70914

15. Major depressive disorder (MDD)Alzheimer’s disease (AD) and MDDDepression appears to represent a risk factor for the development of AD, with severe MDD increasing the risk of AD by five times1,2One study, following >1,300 individuals over a 14-year period, reported that men with a history of depressive symptoms (but interestingly not women) were at twice the risk of developing AD3Shared pathological mechanisms, including the production of inflammatory cytokines, and the activation of the hypothalamic–pituitary–adrenal axis are thought to underlie the association between depression and AD4A recent genome-wide association study has found no evidence of common polygenic structure for AD and MDD, suggesting that the association is not explained by genetics5The association between depression and dementia has lead some to suggest that depression in fact constitutes part of the prodrome of dementia, rather than being an independent risk factor6AD=Alzheimer’s disease; MDD=major depressive disorderCha et al. CNS Neurol Disord Drug Targets 2014;13(10):1740–1749Chen et al. Br J Psychiatry 2008;193(5):373–377Dal Forno et al. Ann Neurol 2005;57(3):381–387Rodrigues et al. Cell Mol Neurobiol 2014;34(7):925–949Gibson et al. Transl Psychiatry 2017;7(4):e1094Mirza et al. Alzheimers Dement 2014;10(5 Suppl):S323–S32915

16. Physical comorbiditiesMajor depressive disorder (MDD)16

17. Major depressive disorder (MDD)Physical comorbidities of MDDThe authors are clear about possible limitations to their study, which include lacking any data about medication usage; it is possible that some of the associations identified in the study are linked to adverse effects of medications, rather than the depression itself1COPD=chronic obstructive pulmonary disorder; GAD=generalised anxiety disorder; MDD=major depressive disorder; PD=panic disorderSchoepf et al. J Psychiatr Res 2014;52:28–3517Prevalence of comorbidities in patients with MDD compared with age-matched controls1

18. Major depressive disorder (MDD)DiabetesIn one large-scale comparison of >400,000 patients with severe mental illness matched to >5 million controls, patients with MDD were 1.4 times more likely to develop type 2 diabetes compared with the general population1In another analysis – a meta-analysis of 18 publications – patients with depression were 1.6 times more likely to develop type 2 diabetes than healthy controls2Importantly, in this analysis a strong association was not seen for patients with diabetes subsequently developing depression (the reverse correlation)2The exact reason for the association between depression and diabetes is unclearMDD=major depressive disorderVancampfort et al. World Psychiatry 2016;15(2):166–174; 2. Mezuk et al. Diabetes Care 2008;31(12):2383–239018

19. Major depressive disorder (MDD)HypertensionIn an analysis of a large claims database, using a sample of >750,000 individuals, the incidence of hypertension in patients with MDD was compared with the general population1The one-year prevalence of hypertension was higher in patients with MDD:(21.2% versus 13.3%, risk ratio: 1.22)a,1Questions remain about depression and hypertension; is it a direct, independent risk factor, or are there other risk factors involved?Behavioural factors relating to depression could contribute to the increased risk of hypertension, as could lifestyle elements such as being overweight, having a more sedentary lifestyle, smoking, and alcohol use1However, lending credence to the idea of a direct connection, symptoms of depression are increasingly being linked to dysregulation of the HPA axis, which is also important for the regulation of blood pressure1Whether the connection between MDD and hypertension is direct or indirect, it is important for treating physicians to consider and monitor blood pressure in patients with MDD1,2aAdjusted risk ratioHPA= hypothalamic–pituitary–adrenal; MDD=major depressive disorder; ns=not significant; RR=risk ratioWu et al. J Psychosom Res 2012;73(3):169–174Patten et al. Psychosom Med 2009;71(3):273–27919Incidence of hypertensionRRp-valueMDDGeneral populationAge 18–391.020.681.70<0.001Age 40–594.484.101.12<0.001Age ≥6013.7211.541.16<0.05Male4.823.151.30<0.001Female3.502.651.12nsIncidence of hypertension in patients with MDD compared with general population1

20. Major depressive disorder (MDD)Cardiovascular diseaseIt has long been recognised that depression confers an increased risk of cardiovascular disease, and of experiencing coronary events1The risk ratio in one meta-analysis was 1.30 versus the general population2There are many potential factors explaining the increased risk, including the sympathetic nervous system, inflammation, platelet activation, and dysregulation of the HPA axis1Demonstrating a direct link between MDD and cardiovascular disease is challenging, because they exist within a cloud of interconnected conditions; for example, MDD appears to increase the risk of hypertension, and diabetes, which both impact on the risk of coronary events1Furthermore, depression is connected with lifestyle elements such as being overweight, having a more sedentary lifestyle, smoking, and alcohol use1,3Nevertheless, there are several potential mechanisms that could mediate the increased cardiovascular risk in patients with MDD1HPA=hypothalamic–pituitary–adrenal axis; MDD=major depressive disorder1. Dhar & Barton. Front Psychiatry 2016;7:332. Gan et al. BMC Psychiatry 2014;14:3713. Wu et al. J Psychosom Res 2012;73(3):169–17420The toxic combination of depression and cardiovascular disease leads to poorer health outcomes for both conditions and escalating health-care costs1

21. Major depressive disorder (MDD)CancerA meta-analysis has shown an increased incidence of cancer in patients with MDD – risk ratio 1.15 versus the general population1When analysed for specific cancers, the increased incidence was only significant for certain types, including lung and liver cancer1Furthermore, meta-analyses have shown that depression appears to be associated with elevated mortality in patients with cancer, but not associated with cancer progression2,3CI=confidence interval; MDD=major depressive disorderJia et al. Public Health 2017;149:138–148; Pinquart & Duberstein. Psychol Med 2010;40(11):1797–1810; Satin et al. Cancer 2009;115(22):5349–536121Because of the lack of large, multi-national studies, and the potential for confounding factors, more research is needed to support the association of depression and cancer1Association between depression and cancer risk1

22. Major depressive disorder (MDD)Summary of the increased risk of comorbidities in patients with MDDaLifetime comorbidity of a major depressive episode and non-affective psychosisRickelt et al. J Affect Disord 2016;203:241–247Dold et al. J Affect Disord 2018;227:254–259Thaipisuttikul et al. Neuropsychiatr Dis Treat 2014;10:2097–2103; Kessler et al. Arch Gen Psychiatry 2005;62(6):593–602Kessler. The prevalence of psychiatric comorbidity. 1997Bron et al. J Affect Disord 2016;197:29–35; Cha et al. CNS Neurol Disord Drug Targets 2014;13(10):1740–1749Chen et al. Br J Psychiatry 2008;193(5):373–377Mezuk et al. Diabetes Care 2008;31(12):2383–2390; Gan et al. BMC Psychiatry 2014;14:371 Wu et al. J Psychosom Res 2012;73(3):169–174 Jia et al. Public Health 2017;149:138–14822ConditionOdds ratio/risk ratioObsessive–compulsive disorder (OCD)Up to 37.51-4Schizophrenia7.05,aPost-traumatic stress disorder (PTSD)6.75Attention deficit hyperactivity disorder (ADHD)4.56Drug dependence 4.35Generalised anxiety disorder3.45NeuropsychiatricConditionOdds ratio/risk ratioAlzheimer’s disease5.07,8Diabetes1.69Cardiovascular disease1.3010Hypertension1.2211Cancer1.1512Physical